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Email:
T.J.Underwood@soton.ac.uk

Professor Tim Underwood BSc (Hons), MBBS, PhD, FRCS (Gen. Surg)

Professor of Gastrointestinal Surgery

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Professor Tim Underwood is Cancer Research UK & Royal College of Surgeons of England Advanced Clinician Scientist Fellow within Medicine at the University of Southampton.

Tim Underwood is Professor of Gastrointestinal Surgery and Head of Cancer Sciences Academic Unit at the University of Southampton. He trained in London and the Wessex region before completing a PhD in Molecular Biology and taking up an NIHR Clinical Lectureship in Surgery in 2008. In 2011 he was awarded a Medical Research Council Clinician Scientist Fellowship and in the same year he won the Association of Surgeons of Great Britain and Ireland prize and gold medal for outstanding performance in the Intercollegiate Specialty Examinations (General Surgery). He became a Cancer Research UK & Royal College of Surgeons of England Advanced Clinician Scientist Fellow in April 2017.

Professor Underwood leads a programme of research studying the role of the tumour microenvironment in cancer development and progression with a particular interest in oesophageal cancer and tumour ecology. His team focus on understanding the molecular determinants of response to chemotherapy and the development of new therapies that target the tumour microenvironment to enhance the efficacy of conventional treatments.  Developing themes include the regulation of antigen presentation in oesophageal cancer and the influence of exercise on response to chemotherapy and the tumour microenvironment across tumour types.  His team develop and apply advanced technologies to understand tumour complexity in oesophageal cancer including highly parallel genome-wide expression profiling of single cells using nanoliter droplets (DropSeq) and the generation of multicellular organoid models.

Professor Underwood is a member of the National Cancer Research Institute (NCRI) Upper GI Clinical Studies Group and Oesophagogastric sub-group.  He is a member of the Steering Committee of the Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS) consortium, a UK-wide collaboration that is defining the genetic landscape of oesophageal adenocarcinoma, including a new molecular classification. He has a portfolio of clinical trial activity in upper GI cancer.

Tim works nationally on behalf of the Royal College of Surgeons of England as Genomics Champion and Site-Specific Lead for oesophageal cancer.  He is part of the NHS England Oesophago-Gastric Cancer Surgery Service Review working group, which is preparing an updated specification for service provision across the NHS.  Internationally, Professor Underwood is co-leading a project to integrate biological parameters into the AJCC (TNM) staging system for oesophageal cancer for the first time.

Qualifications

BSc, Molecular Medicine, University of London (1997)
MBBS, University of London (1998)
MRCS, Royal College of Surgeons of England (2002)
PhD, University of Southampton (2007)
FRCS (Gen. Surg), Royal College of Surgeons of England (2011)

Appointments held

MRC/RCS Clinical Research Training Fellow, Cancer Sciences Division, University of Southampton (2003-2006)

Specialist Registrar, General Surgery, Wessex Deanery (2003-2008)

NIHR Clinical Lecturer in Surgery, Cancer Sciences Division, University of Southampton (2008-2011)

MRC Clinician Scientist, Cancer Sciences Division, University of Southampton (2011- )

Research interests

Mr Underwood’s research has a focus on the development and progression of upper GI cancer, in particular oesophageal cancer. His surgical science interests include minimally invasive surgery and pre and post-operative predictors of outcome after oesophagogastic surgery.

Stromal-epithelial interactions in oesophageal cancer

Oesophageal adenocarcinoma (EAC) is the fastest rising cancer in the UK; the incidence has doubled in men over the last 25 years. At presentation the majority of oesophageal tumours will have invaded through the wall of the oesophagus, meaning that only 20% of patients will be suitable for curative treatment. Early invasion leads to disseminated disease and an overall five year survival of only 7%, one of the lowest of any cancer.

Southampton offers a unique opportunity to perform research in oesophageal cancer. The surgical unit performs over 80 upper gastro-intestinal cancer resections per year and the biomedical research facility is a 2 minute walk from the operating theatre. This allows Mr Underwood’s team to exploit their access to primary tissue for laboratory research; furthermore:

  • Mr Underwood has set up a comprehensive, ethically approved oesophageal tissue bank that contains over 200 patients’ samples including cell isolates, frozen tissue and matched blood from diagnostic endoscopy and oesophageal resections. The tissue bank is linked to a rigorously maintained prospective database that allows biological findings to be correlated with clinico-pathological patient outcomes.
  • The team is able to culture oesophageal epithelial cells and fibroblasts directly from resected specimens.


Molecular studies of carcinogenesis have traditionally been conducted on cells that form the tumour i.e. – epithelial cells and less focus has been placed on the epithelial microenvironment (stroma). An emerging body of evidence suggests that the stroma is important in the initiation and progression of a range of epithelial cancers including skin, breast, prostate and ovary, but little is known about the role of the stroma in oesophageal carcinogenesis. The stroma contains a number of cell types, including fibroblasts, endothelial cells and immune cells, all of which may have a role in tumour progression. Mr Underwood’s research concentrates on cancer associated fibroblasts (CAF) as recent evidence suggests that CAF are fundamental to tumour biology. CAF differ in phenotype from normal fibroblasts, and functional studies indicate that fibroblasts play a role in cancer initiation, progression and metastasis. Information regarding the role of the tumour microenvironment in oesophageal cancer is limited. It is clear that the gene expression profile of stromal cells is altered in EAC and its precursor lesion Barrett’s oesophagus (BE). However, the events required for fibroblast activation, the timing of fibroblast activation in the BE-EAC sequence and the influence that CAF have on EAC progression are yet to be elucidated.

Using a 3D organotypic model developed in the Underwood laboratory the team have shown that primary oesophageal CAF promote invasion compared to normal oesophageal fibroblasts. Moreover, CAF promote the invasion of normal oesophageal squamous cells suggesting that invasion in this model is stromal cell dependent. The team has therefore begun an analysis of candidate molecules which may be responsible for this effect. They have identified several CAF associated candidates, including the TGF-β related gene periostin, on which they have begun a functional analysis.

Department(s)

Cancer Sciences

Affiliate Department(s)

Cancer Sciences Research group

University of Southampton

South Coast Cancer Collaboration - Oesophagogastric (SC3-OG), Lead

National and International responsibilities

NIHR cross disciplinary leadership group
Heartburn Cancer Awareness and Support, Trustee and Director
National Cancer Research Institute (NCRI) Upper GI Clinical Studies Group - Oesophagogastric subgroup – member
The OCCAMS collaboration – lead researcher for Southampton

BM4 and BM5. Ward based teaching for students during their surgical attachment. Developed and delivers trauma scenarios for year 1 BM4 students using the SIMMAN suite. Lectures on trauma and the clinical physiology of shock.

BMedSc Project Supervisor. Offers 2 clinically based projects per year and has supervised previous BMedSc project prize winner.

Professor Tim Underwood
Faculty of Medicine, Room AB215, Mailpoint 801, South Academic Block, University Hospital Southampton, Tremona Road, Southampton, SO16 6YD

Room Number: SGH/CS -B2/MP824

Email:T.J.Underwood@soton.ac.uk

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